2022
Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation
Su KN, Ma Y, Cacheux M, Ilkan Z, Raad N, Muller GK, Wu X, Guerrera N, Thorn SL, Sinusas AJ, Foretz M, Viollet B, Akar JG, Akar FG, Young LH. Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation. JCI Insight 2022, 7: e141213. PMID: 35451373, PMCID: PMC9089788, DOI: 10.1172/jci.insight.141213.Peer-Reviewed Original ResearchConceptsTranscription factorsKey transcription factorMaster metabolic regulatorIon channel subunitsGap junction proteinTranscriptional reprogrammingAMPK deletionProtein kinaseBiological functionsTranscriptional downregulationMetabolic regulatorChannel subunitsIon channelsAMPK expressionMetabolic stressAtrial fibrillationAMPKJunction proteinsElectrical excitabilityHomeostatic roleStructural remodelingConnexinsAtrial ion channelsRemodelingDownregulation
2021
Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8+ T cells during the primary immune response
Levine L, Hiam-Galvez K, Marquez D, Tenvooren I, Madden M, Contreras D, Dahunsi D, Irish J, Oluwole O, Rathmell J, Spitzer M. Single-cell analysis by mass cytometry reveals metabolic states of early-activated CD8+ T cells during the primary immune response. Immunity 2021, 54: 829-844.e5. PMID: 33705706, PMCID: PMC8046726, DOI: 10.1016/j.immuni.2021.02.018.Peer-Reviewed Original ResearchConceptsImmune responseMetabolic stateMass cytometrySingle-cell metabolic analysisSingle-cell resolutionChimeric antigen receptor TDistinct metabolic statesSingle-cell analysisAdvanced lymphoma patientsMetabolic protein expressionListeria monocytogenes infectionImmune cell populationsPrimary immune responseMetabolic proteinsCell signalingOxidative phosphorylationMetabolic regulationLymphoma patientsMemory TMonocytogenes infectionEffector TMetabolic regulatorMetabolic analysisMetabolic adaptationEffector functions
2020
A MicroRNA Linking Human Positive Selection and Metabolic Disorders
Wang L, Sinnott-Armstrong N, Wagschal A, Wark AR, Camporez JP, Perry RJ, Ji F, Sohn Y, Oh J, Wu S, Chery J, Moud BN, Saadat A, Dankel SN, Mellgren G, Tallapragada DSP, Strobel SM, Lee MJ, Tewhey R, Sabeti PC, Schaefer A, Petri A, Kauppinen S, Chung RT, Soukas A, Avruch J, Fried SK, Hauner H, Sadreyev RI, Shulman GI, Claussnitzer M, Näär AM. A MicroRNA Linking Human Positive Selection and Metabolic Disorders. Cell 2020, 183: 684-701.e14. PMID: 33058756, PMCID: PMC8092355, DOI: 10.1016/j.cell.2020.09.017.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytes, BrownAdiposityAllelesAnimalsCell DifferentiationCell LineCells, CulturedDiet, High-FatEnergy MetabolismEpigenesis, GeneticGenetic LociGlucoseHomeostasisHumansHypertrophyInsulin ResistanceLeptinMaleMammalsMetabolic DiseasesMice, Inbred C57BLMice, ObeseMicroRNAsObesityOligonucleotidesSpecies SpecificityConceptsPositive selectionMiR-128Additional genetic elementsCrucial metabolic regulatorAncient adaptationEvolutionary adaptationGenetic elementsMetabolic regulatorGenetic ablationLociMetabolic maladaptationLactase geneAntisense targetingMetabolic disease modelsThrifty phenotypeDisease modelsDiet-induced obesityMetabolic diseasesAbility of adultsMammalsAdaptationGenesMicroRNAsRegulatorSelectionATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration
Mnatsakanyan N, Jonas EA. ATP synthase c-subunit ring as the channel of mitochondrial permeability transition: Regulator of metabolism in development and degeneration. Journal Of Molecular And Cellular Cardiology 2020, 144: 109-118. PMID: 32461058, PMCID: PMC7877492, DOI: 10.1016/j.yjmcc.2020.05.013.Peer-Reviewed Original ResearchConceptsMitochondrial permeability transition poreC subunit ringMitochondrial permeability transitionPermeability transitionRegulator of metabolismPermeability transition poreImportant metabolic regulatorMitochondrial megachannelBiology todayRegulatory mechanismsCentral playerTransition poreMetabolic regulatorMolecular compositionRecent findingsRegulatorDegenerative diseasesPathophysiological roleRecent advancesMegachannelRoleMetabolismMysterious phenomenon
2018
Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome
Yu X, Teng XL, Wang F, Zheng Y, Qu G, Zhou Y, Hu Z, Wu Z, Chang Y, Chen L, Li HB, Su B, Lu L, Liu Z, Sun SC, Zou Q. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. Journal Of Experimental Medicine 2018, 215: 2463-2476. PMID: 30115741, PMCID: PMC6122976, DOI: 10.1084/jem.20180397.Peer-Reviewed Original ResearchConceptsCell metabolismPhosphatase catalytic subunitRapamycin complex 1Component raptorRegulatory T Cell StabilityCatalytic subunitMetabolic programsMechanistic targetPivotal regulatorSignaling mechanismTRAF3IP3Metabolic regulatorMetabolic fitnessCell functionRegulatorLysosomesMetabolismT reg cell functionCell stabilityPP2AcComplexes 1RaptorsSubunitsDeletionStrong antitumor T-cell responsesThe Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut
Schofield WB, Zimmermann-Kogadeeva M, Zimmermann M, Barry NA, Goodman AL. The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut. Cell Host & Microbe 2018, 24: 120-132.e6. PMID: 30008292, PMCID: PMC6086485, DOI: 10.1016/j.chom.2018.06.002.Peer-Reviewed Original ResearchConceptsCarbon starvationStringent responseHuman gut bacterium Bacteroides thetaiotaomicronTricarboxylic acid cycle genesMultiple biosynthetic pathwaysCycle genesCentral metabolismMammalian gutTriggers accumulationBiosynthetic pathwayBacteroides thetaiotaomicronDeficient strainMetabolic regulatorAlpha-ketoglutarate supplementationStarvationAlpha-ketoglutarateC labelingCommensal bacteriaMetabolomic analysisGut microbiomeCommensal bacteriumThetaiotaomicronBacteriaPathwayGutDNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk
Xie W, Kagiampakis I, Pan L, Zhang YW, Murphy L, Tao Y, Kong X, Kang B, Xia L, Carvalho FLF, Sen S, Yen R, Zahnow CA, Ahuja N, Baylin SB, Easwaran H. DNA Methylation Patterns Separate Senescence from Transformation Potential and Indicate Cancer Risk. Cancer Cell 2018, 33: 309-321.e5. PMID: 29438699, PMCID: PMC5813821, DOI: 10.1016/j.ccell.2018.01.008.Peer-Reviewed Original ResearchConceptsDevelopmental genesDNA methylation patternsPromoter hypermethylation eventsEpigenetic patternsMethylation gainMethylation patternsMethylation changesHypermethylation eventsEpigenetic changesTissue agingSenescenceMetabolic regulatorTissue typesGenesTransformation potentialCellsHypermethylationRegulatorCancer risk
2017
Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport
Nagarajan A, Dogra SK, Sun L, Gandotra N, Ho T, Cai G, Cline G, Kumar P, Cowles RA, Wajapeyee N. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport. Molecular Cell 2017, 67: 685-701.e6. PMID: 28803777, PMCID: PMC5567863, DOI: 10.1016/j.molcel.2017.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntineoplastic AgentsApoptosis Regulatory ProteinsAryldialkylphosphataseCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementCell ProliferationEnergy MetabolismFemaleForkhead Box Protein O3Gene Expression Regulation, NeoplasticGlucoseGlucose Transporter Type 1HumansLiver NeoplasmsLung NeoplasmsMaleMice, NudeMutationPancreatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)RNA InterferenceSignal TransductionTime FactorsTranscription, GeneticTransfectionTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsPDAC tumor growthGlucose transportCellular starvation responsesParaoxonase 2Glutamine metabolism pathwayNew metabolic regulatorPDAC tumor samplesShort hairpin RNATumor growthStarvation responseMetabolic genesTranscriptional targetsProtein kinaseTractable pathwayPancreatic cancer growthGenetic activationMetabolism pathwaysHairpin RNAMetabolic regulatorNew modulatorsHuman cancersPancreatic ductal adenocarcinomaMetabolic deregulationAMPKCancer growth
2014
Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α
Shi X, Cheng Q, Xu L, Yan J, Jiang M, He J, Xu M, Stefanovic-Racic M, Sipula I, O'Doherty RM, Ren S, Xie W. Cholesterol Sulfate and Cholesterol Sulfotransferase Inhibit Gluconeogenesis by Targeting Hepatocyte Nuclear Factor 4α. Molecular And Cellular Biology 2014, 34: 485-497. PMID: 24277929, PMCID: PMC3911511, DOI: 10.1128/mcb.01094-13.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBlotting, WesternCarcinoma, HepatocellularCell Line, TumorCell NucleusCells, CulturedCholesterol EstersCoenzyme A LigasesColforsinDiet, High-FatGene ExpressionGluconeogenesisGlucoseHepatocyte Nuclear Factor 4HumansInsulin ResistanceMiceMice, Inbred C57BLMice, ObeseMice, TransgenicObesityReverse Transcriptase Polymerase Chain ReactionSulfotransferasesConceptsDiet-induced obesityHepatocyte nuclear factor 4αNuclear factor 4αCholesterol sulfateLeptin-deficient miceTreatment of micePotential therapeutic targetPotential therapeutic agentExpression of SULT2B1bMetabolic abnormalitiesObese miceMetabolic disordersImportant metabolic regulatorGlucose metabolismTherapeutic targetTransgenic miceFed stateHepatic gluconeogenesisTherapeutic agentsMiceTransgenic overexpressionSULT2B1bMetabolic regulatorFunctional homeostasisInhibits gluconeogenesis
2013
Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaRecurrent hypoglycemiaHypoglycemic conditionsIntensive insulin therapyTight glycemic controlType 2 diabetesInsulin therapyGlycemic controlBrain metabolismElevated lactateNeuronal metabolismRodent modelsNeuronal activityGlucose metabolismHypoglycemiaLactate uptakeNeuronal functionType 1Metabolic regulatorOxidative capacityModest incrementLactateMetabolismUnexpected findingBrain
2012
AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart
Zaha VG, Young LH. AMP-Activated Protein Kinase Regulation and Biological Actions in the Heart. Circulation Research 2012, 111: 800-814. PMID: 22935535, PMCID: PMC4397099, DOI: 10.1161/circresaha.111.255505.BooksConceptsAMPK pathwayProtein kinase regulationCellular fuel gaugeStress-activated kinasesRegulation of AMPKMaster metabolic regulatorNovel molecular mechanismBiological actionsKinase regulationDiverse biological actionsAMPK regulationProtein kinaseMolecular mechanismsMetabolic regulatorFuel gaugeImportant biological actionsRecent discoveryKinaseAMPKRegulationNew insightsPharmacological activationPathwayImportant roleTherapeutic potential
2009
A Crystallized View of AMPK Activation
Young LH. A Crystallized View of AMPK Activation. Cell Metabolism 2009, 10: 5-6. PMID: 19583947, DOI: 10.1016/j.cmet.2009.06.008.Commentaries, Editorials and LettersConceptsAMPK activationAMPK catalytic subunitKey metabolic regulatorAutoinhibitory sequenceCatalytic subunitKinase domainProtein kinaseMetabolic regulatorStructural interactionsCrystallized viewNovel therapeutic approachesActivationKinaseSubunitsRegulatorEnhanced understandingRecent workSequenceTherapeutic approachesMolecular mechanicsDomain
2008
Gene Expression Profiling Reveals Putative HOXA10 Downstream Targets in the Periimplantation Mouse Uterus
Vitiello D, Pinard R, Taylor HS. Gene Expression Profiling Reveals Putative HOXA10 Downstream Targets in the Periimplantation Mouse Uterus. Reproductive Sciences 2008, 15: 529-535. PMID: 18579861, PMCID: PMC3107854, DOI: 10.1177/1933719108316911.Peer-Reviewed Original ResearchConceptsMicroarray analysisHoxA10 target geneSignal transduction factorsGene expression profilingTumor-associated calcium signal transducer 2Calcium signal transducer 2Transcription factorsHOXA10 expressionTarget genesCell adhesion moleculeCandidate genesExpression profilingCellular ontogenyDownstream targetsMolecular mechanismsSignificant genesMolecular markersPeriimplantation mouse uterusTransduction factorsGenesHOXA10 overexpressionMetabolic regulatorFurther characterizationAdhesion moleculesReal-time reverse transcriptase-polymerase chain reaction
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